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OBJECTIVES: In view of previous studies demonstrating hyperleptinemia in uremic and hemodialysis patients, the aims of the present study were to determine whether serum leptin levels are elevated in peritoneal dialysis (PD) patients, to establish whether leptin is significantly removed by PD, and to elucidate the relationship of plasma leptin to body composition, dietary intake, nutritional indices, and dialysis adequacy. DESIGN: Cross-sectional analysis of PD patients and matched healthy controls. SETTING: Tertiary-care institutional dialysis center. PARTICIPANTS: The study included 49 PD patients [35 women and 14 men; median age 63 years, interquartile range (IQR) 49.5-68.5 yr; body mass index (BMI) 25.5 +/- 0.8] and 27 controls (11 men and 16 women; median age 42 years, IQR 34.8-51; BMI 27.2 +/- 0.9). For evaluation of leptin clearance, 8 patients receiving nocturnal intermittent PD were also evaluated. MAIN OUTCOME MEASURES: The primary outcome measure was plasma leptin concentration. Dialysate leptin concentration was also measured in 7 patients. RESULTS: Serum leptin levels were significantly higher (p < 0.01) in patients (males: median 11 ng/mL, IQR 9-19 ng/mL; females: 53 ng/mL, 19.5-128 ng/mL) compared with controls (males: 5.5 ng/mL, 4-9.5 ng/mL; females: 12 ng/mL, 9.8-17.3 ng/mL). Leptin levels in both groups correlated positively with BMI (r = 0.64 and 0.60, respectively; p < 0.0001) and with percentage body fat determined by dual-energy x-ray absorptiometry (r = 0.86 and 0.82, respectively; p < 0.01). Dialysis patients exhibited a greater increase in serum leptin for any given increase in BMI. No significant correlation was observed between leptin concentration and residual renal function, dialysis adequacy (Kt/V), dietary protein or caloric intake, or serum levels of albumin, prealbumin, C-reactive protein, glucose, and insulin-like growth factor-I. Although leptin was detectable in peritoneal dialysate after a 6-hour dwell (median 4.2 ng/mL, IQR 1.1-8.5 ng/mL, n = 8), serum leptin levels were not appreciably lowered following intermittent PD via an automated cycler (63.9 +/- 19.3 ng/mL vs 57.6 +/- 20.5 ng/mL, p = NS, n = 8). CONCLUSIONS: Serum leptin levels are elevated in PD patients and are not appreciably cleared by PD. Although hyperleptinemia correlates poorly with dialysis adequacy and protein intake, a strong and significant relationship was maintained between serum leptin and fat mass. Serum leptin could therefore serve as a useful clinical marker of body fat content in PD patients.